Pulmonary hypertension (“PH”) is a pathological elevation of blood pressure within the pulmonary circulation which is initiated with inflammation and changes in endothelial cells lining the pulmonary artery. As discussed herein, PH is divided into five groups based on its causes, with each group indication showing mean pressure in the pulmonary arteries of greater than 25 mmHg at rest or 30 mmHg during physical activity, with normal pulmonary artery resting mean pressure being within a range of 8-20 mmHg. A form of PH, pulmonary arterial hypertension (“PAH”), is a chronic, progressive and ultimately fatal disease which includes symptoms such as increased pulmonary vascular resistance of the lung microvasculature, intimal hyperplasia, smooth muscle hypertrophy and in situ thrombosis. Whether caused by a single or via multiple factors, one common thread to PAH is marked PAEC dysfunction, where progression of the disease associates with notable increases in vasoconstrictor and proliferation mediators while showing a concomitant decrease in vasodilator and antiproliferative agents.
Pulmonary arterial hypertension is notoriously difficult to successfully treat, leading, in part, to its poor prognosis. A first line therapy for treating PAH includes ET-1 receptor antagonists (“ERAs”), which either selectively inhibit the ETA membrane receptor (e.g., sitaxsentan and ambrisentan) localized to pulmonary arterial smooth muscle cells, or antagonists which non-selectively bind both the ETA and ETB membrane receptor (e.g., besentan); the ETB receptor being localized to both pulmonary arterial smooth muscle cells and pulmonary arterial endothelial cells. Another primary therapy includes selective inhibitors of phosphodiesterase-5 (e.g., sildenafil). Antagonists of PDE-5 are thought to prolong NO availability, a potent pulmonary vasodilator. One late stage therapy includes administration of a prostacyclin analogue (including epoprostenol, a synthetic form of the natural prostaglandin derivative PGI2 provided as a sodium salt). Prostacylcin is a potent vasodilator with antiproliferative characteristics that shows marked decrease in patients diagnosed with PAH. Unfortunately, these prostacyclin analogues (also including treprostinil [subcutaneous injection] and iloprost [via inhalation]) possess such a short half life (about 6 minutes) that the drug must be administered intravenously over a prolonged time frame. Although these therapies can be used, great variability exists among patients in their response. This variability includes dramatically greater or lesser response to therapy in individual patients versus the response that is expected based on other prognostic factors. Pulmonary arterial hypertension is further classified into either an “associated” form, where there is an identifiable cause for the pulmonary vascular changes or two related diseases known as idiopathic PAH (IPAH), where no identifiable cause exists, and familial PAH (FPAH), in which the disease is related to mutations in the BMPR2 gene. One of the major challenges in establishing a therapeutic regimen is that different patients respond differently to first-line therapies, specifically ERAs and PDE-5 antagonists, and it is presently impossible to predict which class of drugs will be more effective in a newly diagnosed PAH patient. The present invention addresses these clinical needs through isolation of PAECs from individual patients suffering from pulmonary vascular disease, including PAECs from patients diagnosed with or showing symptoms of PAH, thus allowing for methods utilizing such PAECs to provide diagnostic and prognostic indications for personalized pharmacotherapy to treat progressing pulmonary vascular disease states, as well as using PAECs described herein to screen for drugs useful in the treatment of pulmonary vascular disease, and providing primary and secondary PAECs for generation of phenotype-specific immortalized cell lines.